POS0120 SAFETY AND EFFICACY OF SUBCUTANEOUS (S.C.) DOSE IANALUMAB (VAY736; ANTI-BAFFR mAb) ADMINISTERED MONTHLY OVER 28 WEEKS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Authors: J. Cortés-Hernández, S. Ignatenko, A. Gordienko, N. Agmon-Levin, P. Narongroeknawin, K. Romanowska -Prochnicka, N. Shen, H. Ciferská, M. Kodera, J. C. C. Wei, P. Leszczynski, J. L. Lan, R. Wojciechowski, T. Tarr, E. Vishneva, Y. H. Chen, Y. Kaneko, S. Finzel, A. Hoi, M. Okada, A. Koolvisoot, S. S. Lee, L. Dai, H. Kaneko, B. Rojkovich, L. Sun, E. Zotkin, B. Magallares, T. Sengupta, C. Sips, S. Oliver
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ianalumab (VAY736) is a novel defucosylated, human IgG1 mAb targeting the receptor for B cell Activating Factor of TNF Family (BAFF-R), providing both enhanced antibody-dependent cellular cytotoxicity-mediated depletion of B cells and blockade of BAFF:BAFF-R signaling that drives B cell differentiation, proliferation and survival. <h3>Objectives</h3> Evaluate safety and efficacy of ianalumab in patients with active SLE. <h3>Methods</h3> Multi-center, randomised, parallel group, double-blind trial consisting of 2 separate, placebo-controlled treatment cohorts for ianalumab and for iscalimab (CFZ533; anti-CD40 mAb) randomised 1:1 between active:placebo. Patients (ianalumab cohort n= 67, iscalimab cohort n= 40) with ANA ≥1:80 and meeting ≥4/11 ACR 1997 SLE classification criteria, with SLEDAI-2K score ≥6 and BILAG-2004 ≥1 'A' or two 'B' scores that included activity in either mucocutaneous and/or musculoskeletal domains were enrolled from 19 Dec 2018 through 31 Jan 2022. Here we report interim analysis results for ianalumab treatment cohort (active n=34, placebo n=33) completing the 28-week blinded treatment period, which comprised of monthly s.c. injection of ianalumab 300 mg or placebo. Outcomes were measured at baseline (BL) and weeks (w) 4, 8, 12, 16, 24 and 28. The primary w28 outcome was proportion of patients meeting composite endpoint requirements consisting of patients who both achieved SRI-4 and also tapered predniso(lo)ne ≤5 mg/d or ≤ BL dose, whichever was lower, by w16 and kept within that range to w28. Other outcomes included safety and tolerability, incidence of BILAG-2004 moderate or severe flares, proportion of patients achieving Lupus Low Disease Activity State (LLDAS), change from BL in SLEDAI-2K and BILAG-2004, physician/patient global visual analog scale (VAS) assessments and laboratory markers of inflammation and immune activation. Post-w28 patients received open-label ianalumab for 20w, then safety follow up off treatment up to 2 years (y). <h3>Results</h3> Median age was 42y and 39y for ianalumab and placebo arms, respectively, with 8 males (ianalumab: 2, placebo: 6). BL median (<i>range</i>) values for ianalumab and placebo arms, respectively, were: SLEDAI-2K scores 10 (<i>6-32</i>) and 10 (<i>4-18</i>), and predniso(lo)ne 10.0 mg (<i>0-30.0</i>) and 10.0 mg (<i>2.5-27.5</i>). Proportion of patients treated with ianalumab or placebo, respectively, achieving SRI-4 at w28 (Figure 1) was 70.6% (n=24) vs. 24.2% (n=8), and also meeting composite endpoint (Figure 1 insert): 44.1% (n=15) vs. 9.1% (n=3). Ianalumab showed benefit vs placebo in other outcomes (Table 1) for incidence moderate or severe flare, time to moderate or severe flare, achieving w28 LLDAS, and serum levels of complement and autoantibodies. No drug-related SAEs were reported with ianalumab during blinded or subsequent 20w open-label treatment. There were 2 AE-related dropouts occurring during open-label treatment, one in ianalumab arm (morphoea) and one with placebo (worsening of SLE). Pandemic-related discontinuations included one from each arm during the blinded treatment period, and 2 occurring post-w28 in the ianalumab arm: one each in open label and during safety follow up. <h3>Conclusion</h3> Treatment of SLE with ianalumab was well tolerated and met the composite primary endpoint of SRI-4 response with sustained steroid reduction, with additional benefits seen across other study endpoints. These positive results support further evaluation of ianalumab in SLE. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Josefina Cortés-Hernández: None declared, Stanislav Ignatenko: None declared, Alexander Gordienko: None declared, Nancy Agmon-Levin: None declared, Pongthorn Narongroeknawin Speakers bureau: Novartis (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Grant/research support from: AstraZeneca, Galapagos, Glaxo-Smith Kline, Novartis (Researcher), Katarzyna Romanowska -Prochnicka: None declared, Nan Shen: None declared, Hana Ciferská: None declared, Masanari Kodera: None declared, James Cheng-Chung Wei: None declared, Piotr Leszczynski Speakers bureau: AbbVie/Abbott, AstraZeneca, Novartis, Roche, UCB ((includes speakers bureau, symposia, and expert witness)), Grant/research support from: AbbVie/Abbott, Novartis, Roche, UCB, Joung Liang Lan: None declared, Rafal Wojciechowski Speakers bureau: Eli Lilly, Novartis (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Tunde Tarr: None declared, Elena Vishneva: None declared, Yi-Hsing Chen: None declared, Yuko Kaneko Speakers bureau: Speaker/Honoraria (includes speakers bureau, symposia, and expert witness: AbbVie/Abbott, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, AYUMI Pharmaceutical K. K., Bristol-Myers Squibb(BMS), Chug- Pharm, Chug-Pharm, Eisai, Eli Lilly, Gilead, GlaxoSmithKlein(GSK), Janssen, Novartis, Pfizer, Tanabe Mitsubishi Pharma, UCB Japan, Consultant of: Advisor or Review Panel Member: AbbVie/Abbott, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, AYUMI Pharmaceutical K. K., Bristol-Myers Squibb(BMS), Chug- Pharm, Chug-Pharm, Eisai, Eli Lilly, Gilead, GlaxoSmithKlein (GSK), Janssen, Novartis, Pfizer, Tanabe Mitsubishi Pharma, UCB Japan, Stephanie Finzel Speakers bureau: AbbVie/Abbott, Amgen, Galapagos, Novartis, UCB (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Consultant of: Amgen, Novartis, Novonordisk (Advisor or Review Panel Member), Alberta Hoi Speakers bureau: Sandoz, UCB, Janssen (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Consultant of: AbbVie/Abbott (Consultant, Professional service), AstraZeneca, Pfizer (Consultant), Janssen (Consultant, Sponsor of Australian Lupus Registry &amp; Biobank), Grant/research support from: AstraZeneca, Merck Serono (Grant/Research Support), Masato Okada: None declared, Ajchara Koolvisoot: None declared, Shin-Seok Lee: None declared, Lie Dai: None declared, Hiroshi Kaneko: None declared, Bernadette Rojkovich: None declared, Lingyun Sun: None declared, Evgeniy Zotkin: None declared, Berta Magallares: None declared, Tirtha Sengupta Employee of: Novartis, Carole Sips Shareholder of: Novartis (Stock options or bond holdings in a for-profit corporation or self-directed pension plan), Employee of: Novartis, Stephen Oliver Shareholder of: Novartis (Stock options or bond holdings in a for-profit corporation or self-directed pension plan), Employee of: Novartis.